转铁蛋白饱和度升高和血色病基因型与糖尿病患者全因及死因特异性死亡率的关系：两项一般人群研究。

Total and cause-specific mortality by elevated transferrin saturation and hemochromatosis genotype in individuals with diabetes: two general population studies.

机构信息

Corresponding author: Christina Ellervik,

出版信息

Diabetes Care. 2014 Feb;37(2):444-52. doi: 10.2337/dc13-1198. Epub 2013 Oct 15.

DOI:10.2337/dc13-1198

PMID:24130348

Abstract

OBJECTIVE

Mortality is increased in patients with hereditary hemochromatosis, in individuals from the general population with increased transferrin saturation (TS), and also in patients with type 1 diabetes and increased TS from a highly specialized diabetes clinic. Thus, we have recommended targeted screening for TS in specialized diabetes clinics. Whether mortality is also increased in individuals from the general population with diabetes and increased TS is unknown.

RESEARCH DESIGN AND METHODS

In two Danish population studies (N = 84,865), we examined mortality according to baseline levels of TS and hemochromatosis genotype (HFE) G → A substitution at nucleotide 845 in codon 282 (C282Y/C282Y) in individuals with diabetes (type 1, N = 118; type 2, N = 3,228; total, N = 3,346).

RESULTS

The cumulative survival rate was reduced in individuals with diabetes with TS ≥50% vs. <50% (log-rank; P < 0.0001), with median survival ages of 66 and 79 years, respectively. The hazard ratio (HR) for TS ≥50% vs. <50% was 2.0 (95% CI 1.3-2.8; P = 0.0004) for total mortality overall (and similar for men and women separately); 2.6 (1.3-5.4; P = 0.008) for neoplasms; and 3.4 (2.0-6.0; P = 0.00002) for endocrinological causes. A stepwise increased risk of total mortality was observed for stepwise increasing TS (log-rank test, P = 0.0001), with an HR for TS ≥70% vs. TS <20% of 4.8 (2.0-12; P = 0.0006). The HR for total mortality in individuals with diabetes for C282Y/C282Y versus wild type/wild type was 3.3 (1.04-10; P = 0.04), and for C282Y/C282Y and TS ≥50% versus wild type/wild type and TS <50% was 6.0 (1.5-24; P = 0.01). Six percent of these premature deaths can possibly be avoided by early screening for TS or HFE genotype.

CONCLUSIONS

Individuals with diabetes, ascertained in the general population, with increased TS or HFE genotype have a twofold to sixfold increased risk of premature death.

摘要

目的

遗传性血色素沉着症患者、转铁蛋白饱和度（TS）升高的一般人群个体以及 1 型糖尿病患者和来自专门糖尿病诊所的 TS 升高的患者死亡率均增加。因此，我们建议在专门的糖尿病诊所进行 TS 的靶向筛查。但具有糖尿病和 TS 升高的一般人群个体的死亡率是否也会增加尚不清楚。

研究设计和方法

在两项丹麦人群研究中（N=84865），我们根据基线 TS 水平和铁调素基因（HFE）C282 密码子 282 处核苷酸 845 的 G→A 取代（C282Y/C282Y），在患有糖尿病的个体（1 型，N=118；2 型，N=3228；总计，N=3346）中检查了死亡率。

结果

TS≥50%与<50%相比，糖尿病患者的累积生存率降低（对数秩检验；P<0.0001），中位生存年龄分别为 66 岁和 79 岁。TS≥50%与<50%相比，总死亡率的 HR 为 2.0（95%CI 1.3-2.8；P=0.0004）（男女之间相似）；肿瘤为 2.6（1.3-5.4；P=0.008）；内分泌原因为 3.4（2.0-6.0；P=0.00002）。TS 逐渐升高与总死亡率的风险逐渐增加呈正相关（对数秩检验，P=0.0001），TS≥70%与 TS<20%的 HR 为 4.8（2.0-12；P=0.0006）。与野生型/野生型相比，糖尿病患者的 C282Y/C282Y 总死亡率 HR 为 3.3（1.04-10；P=0.04），C282Y/C282Y 和 TS≥50%与野生型/野生型和 TS<50%的 HR 为 6.0（1.5-24；P=0.01）。通过早期筛查 TS 或 HFE 基因型，这些早逝中有 6%可能是可以避免的。